Elevated plasma total homocysteine and C677T mutation of the methylenetetrahydrofolate reductase gene in patients with spina bifida

Total plasma homocysteine (tHcy) was significantly higher in 28 children with spina bifida (median 6.05 mu mol/l) as compared with 76 controls (median 4.94 mu-mol/l). This difference was confined to a subgroup of patients (16/28) with one or two C677T-mutated alleles in the methylenetetrahydrofolate reductase gene. Since we found no significant difference between patients and controls in serum folate, erythrocyte folate, serum cobalamin or serum methylmalonic acid, which were within the normal range for both patients and controls, the elevated tHcy could not be attributed to vitamin deficiencies. Our findings point to an additional genetic defect involving folate-dependent enzymes in a subgroup of patients with neural-tube defects.